This is a request to continue studies that began over 26 years ago (the grant underwent a number change on my move to Dallas 21 years ago) on mechanisms of antibody diversity. Two new models allow us to challenge certain approaches to the developing repertoire: the minilocus transgenic mouse (developed under the auspices of this grant), and the human germinal center B cell (which we can now isolate from tonsils with ease). These two models provide us with the opportunity to challenge existing notions of diversity including insertion/deletion events and the utilization of the DIR gene segments. This is an amended application which attempts to deal with the major criticisms the study section found in the original: 1) the proposal is unfocused, 2) the issues being addressed are relatively uncommon, and 3) the approaches described are not likely to lead to an understanding of the underlying mechanisms. Hopefully the amended application will addresses each of these (and other issues) in a direct and satisfactory manner.